Polymerizable yellow dyes and their use in opthalmic lenses

ABSTRACT

Novel polymerizable yellow dyes are disclosed. Additionally, novel and known dyes are used to block or lower the intensity of blue light transmitted through ocular lenses and other windows.

FIELD OF THE INVENTION

This invention relates to polymeric yellow dyes and their use inophthalmic lenses. In particular, this invention relates topolymerizable yellow dyes of the azo family in "blue-blocking"ophthalmic lenses.

BACKGROUND OF THE INVENTION

The assessment of optical hazards in recent years has led to therecognition of the possible hazards to the retina associated with bluelight (400-500 nm). If the blue light hazard is a real threat to vision,then the UV/visible transmission characteristics of ophthalmic lenses,and intraocular lenses (IOLs) in particular, should be modified toprovide adequate protection from blue light hazards encountered in theenvironment.

In the ambient environment solar radiation is the primary hazard tovision. The sun freely emits UV, visible and IR radiation much of whichis absorbed by the atmosphere. The solar radiation that is transmittedthrough the atmosphere and reaches the earth's surface consists of UV-Bradiation (230-300 nm), near UV or UV-A radiation (300-400 nm), visiblelight (400-700 nm) and near IR radiation (700-1400 nm). The ocular mediaof man in its normal, healthy state freely transmits near IR and most ofthe visible spectrum to the retina, but UV-B radiation is absorbed bythe cornea and does not reach the retina. The transmission of near UVand the blue portion of the visible spectrum can be absorbed by thecrystalline lens depending on age.

The human crystalline lens changes its UV and visible transmissioncharacteristics as it ages. In infancy the human lens will freelytransmit near UV and visible light above 300 nm, but with further agingthe action of UV radiation from the environment causes the production ofyellow pigments, fluorogens, within the lens. By age 54 the lens willnot transmit light below 400 nm and the transmission of light between400 and 500 nm is greatly diminished. As the lens ages it continuouslydevelops a yellow color, increasing its capacity to filter out near UVand blue light. Therefore, after cataract removal the natural protectionprovided by the aged human lens is also removed. If the cataract isreplaced by an IOL, usually UV protection is provided, but blue lightprotection is still lacking.

The use of conventional yellow dyes, such as commercially available4-phenylazophenol (Solvent Yellow 7), 2-(2'-methyl)-phenylazo-4-methylphenol (Solvent Yellow 12) and N-(4-phenylazo)phenyl diethanol amine(Solvent Yellow 58), in IOLs to block blue light is not desirablebecause these dyes are not bound to the lens material and thus may leachout of the IOL after it is inserted in the eye. These nonbonded dyesalso cause problems in the manufacture of polymer lenses that areextracted with a solvent after they are formed. In this extraction step,the solvent may remove up to 90% of the non-bonded dye from the lens.

Japanese Kokai Patent Application No. Hei 1[11989]-299,560 ("MenikonApplication") claims an intraocular lens material characterized by apolymerizable ultraviolet light absorber having a polymerizable groupselected from an acrylol group, a methacrylol group, a vinyl group, anallyl group, and an isopropenyl group, and a polymerizable dye having apolymerizable group selected from an acryloyl group, an allyl group, andan isopropenyl group, which are copolymerized with other polymerizablelens-forming monomer components. Also taught by the Menikon Applicationare polymerizable dyes having a polymerizable group selected frommethacryloyl groups, vinyl groups, and acryl groups. The MenikonApplication lists numerous formulas representing hundreds of dyes. Asexamples of the polymerizable dyes of the azo system, the MenikonApplication lists those of the general formula: ##STR1## where X₁₇ maybe, among others, any of the groups represented by: ##STR2## R¹ is --Hor --CH₃ ; R₂₃ may be, among others, --H, --OH, or a halogen atom;

R₂₄ may not be H, but may be --OH, --CH₃, --C₂ H₅, --OCH₃, --OC₂ H₅, andhalogen atoms;

k, m, l, and n are integers of 0 or 1;

R₂₅ may be, among others, a benzene derivative substituted with C₁ -C₈alkyl groups;

R₂₆ is --H, or C₁ to C₃ lower alkyl; and

Y₁₁ and Y₁₂ are --NH-- or --O--.

The azo dyes taught in the Menikon Application suffer the followingdisadvantages, however. Directly attaching reactive acrylic/methacrylicgroups or other electron-withdrawing groups, such as carbonyl,carboxylic acid, or ester groups, to the dye moiety weakens dye strengthand may change dye color.

The effect of electron-withdrawing groups on the color and relativestrength of a yellow dye can be quite pronounced. For example, theyellow dye known as Solvent Yellow 58 is converted into a red dye,Pigment Red 100, solely by the addition of a carboxylic acid groupdirectly bonded to the phenylazophenyl dye moiety. ##STR3##

There is only one case in which the Menikon Application allows anacrylic/methacrylic group not directly bound to the azo dye moiety by anelectron-withdrawing group. This case requires instead that an aminogroup be directly attached to the dye moiety. Even though amino azo dyesare useful, they are less desirable than phenolic azo dyes because theamino group accelerates the decomposition of peroxide initiators, suchas those used in conventional free-radical polymerization processes.

Another example of dyes based on the amino azo system are the polymericcolorants based on acrylated chromophores of the type ##STR4## whereinR=CH₃ or H; and the Ar group is phenyl, naphthyl, etc. Guthrie,"Polymeric Colorants," Rev. Prog. Color Relat. Topics, Vol. 20, 40-52(1990). Substituents may be added to the aromatic groups to providevariations in color and other physical properties. The works of variouspeople am summarized in this review article. Some of the work reviewedincludes reactive azo dyes containing methacrylate, acrylate, epoxideand vinyl ester functionalities in the following applications andstudies: optical recording materials, the non-linear opticalsusceptibility of copolymers containing acrylic azo monomers and methylmethacrylate, and the determination of copolymerization parameters andreactivity ratios for the copolymerization of azo dye monomerscontaining a methacryloyl functionality with styrene and with methylmethacrylate.

What is needed are additional polymerizable yellow dyes which are easilysynthesized from commercially available dyes or other starting materialsand which, when incorporated in ophthalmic lenses, will not be extractedout of the lens during solvent extraction or leach out of the lens afterinsertion in the eye.

SUMMARY OF THE INVENTION

The polymerizable yellow dyes of the invention are soluble in organicmonomers, such as acrylic/methacrylic monomers, and contain in theirchemical structure one or more acrylic or methacrylic functional groupswhich are reactive towards free radical polymerization. These dyes, whenpolymerized with organic monomers capable of forming a transparentmaterial, will be bonded to the polymer and thus greatly reduce theamount of dye which can leach out of the material. As a result, thesedyes can be used in transparent materials to decrease the intensity ofblue light transmitted through them. These transparent materials withone or more of the bondable yellow dyes incorporated in them may beextracted with organic solvents to remove unreacted monomers, lowmolecular weight oligomers and low molecular weight polymers, as well asother impurities, and then used to make ocular lenses such asintraocular lenses (IOLs), contact lenses, eyeglasses and other windows.These transparent materials containing yellow dye may also be used tomake lens coating materials.

Although like compounds can be expected to copolymerize more efficientlythan unlike compounds, it has now been found that polymerizable yellowdyes having one or more polymerizable acrylate or methacrylate groupswhich have been copolymerized with one or more lens-forming acrylate ormethacrylate monomers are much more efficiently incorporated into thepolymeric lens materials than yellow dyes having other types ofpolymerizable groups, such as vinyl groups.

Additionally, it has now been found that polymerizable yellow dyes ofthe azo family which do not contain electron-withdrawing groups directlyattached to the dye moiety are much stronger yellow dyes than thosewhich do. Acrylic/methacrylic yellow dyes which do not have thepolymerizable group directly bonded to the dye moiety are thereforestronger than those which do.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 show the transmittance of acrylic/methacrylic ophthalmiclens materials containing various yellow dyes.

FIG. 3 presents a polymerization incorporation efficiency comparison offour dye compounds.

DETAILED DESCRIPTION OF THE INVENTION

The polymerizable yellow dyes of the present invention are based on theazo dye system and contain polymerizable acrylate/methacrylate groups.These dyes are characterized by a spacing group which separates thepolymerizable acrylate/methacrylate group from the dye moiety. Thesedyes are further characterized by the absence of an electron-withdrawinggroup directly attached to the dye moiety.

As used herein, "dye moiety" refers to the portion of the dye moleculeprimarily responsible for causing the dye's intense color. In thisinvention, the dye moiety is thus the phenyl-azo-phenyl (Ph--N═N--Ph)portion of the polymerizable yellow dye structure.

The spacing groups of this invention may be any group which separates,by means of covalently bonded atoms, the dye moiety from thepolymerizable acrylic/methacrylic group. The spacing group separates thedye moiety from the acrylic/methacrylic group in such a way as tominimize the effect of the acrylic/methacrylic group on dye strength andcolor. The minimum effect on dye strength and color is achieved bydirectly attaching the spacing group to the dye moiety with anon-electron-withdrawing residue.

Preferred spacing groups of the present invention are those of theformula: ##STR5## where R³ is directly attached to the dye moiety andconsists of an alkyl group of up to 6 carbon atoms;

R⁴ is an acylic organic spacing group of up to 10 atoms which iscomposed of carbon, hydrogen, silicon, oxygen, nitrogen, phosphorous,sulfur, chloride, bromine, or fluorine alone or in any combination;

X=O, NH, NR⁵ ;

R⁵ =C₁ to C₁₀ alkyl;

d, e, g, and h independently=an integer from 0 to 4; and

c and f independently=an integer from 1 to 4.

Electron-withdrawing groups are not permitted to be covalently bonded tothe dye moiety because they can weaken the strength of the yellow dyeand, in some cases, change the absorption nature of the dye sufficientlyto cause a change in color. Examples of electron-withdrawing groupswhich are not permitted to be directly attached to the dye moietyinclude carbonyl groups, such as those found in ketones; carboxylic acidesters; amides; imines; immides; imminic acid esters (especiallyanalogues derived from 1,3,5-triazeno systems); ureas; urethanes; and soon.

The novel dye compounds of the present invention includeacrylates/methacrylates of the formula: ##STR6## wherein R=H or CH₃ ;

R¹ =H, C₁ to C₂₀ alkyl, OCH₃, OC₂ H₅, OC₃ H₇, or OC₄ H₉ ;

a and b independently=the integer 1 or 2;

R² =R¹, OH, NH₂, NHR⁵, N(R⁵)₂, SH, SR⁵, OR⁵, OSi(R⁵)₃ or Si(R⁵)₃ ; and

R³, R⁴, R⁵, X, c, d, e, f, g and h are as defined above.

The preferred compound of Formula 1 isN-2-[3-(2'-methylphenylazo)-4-hydroxyphenyl]ethyl methacrylamide:##STR7##

Compounds of Formula 1 may be prepared by starting with a phenolic,aniline, or other substituted benzene compound containing an organicspacing group terminated by one or more amino or hydroxyl moieties. Oneskilled in the art could form a reaction with methacrylic anhydride,acrylic anhydride, acryloyl chloride, methacryloyl chloride or othersuitable acrylic/methacrylic reagent to give an intermediateacrylic/methacrylic compound. If necessary to induce the reactivity ofthe side chain amino or hydroxyl group, strong bases, such as sodiumhydride or butyllithium, may be employed; weaker bases, such astriethylamine, may also be useful.

The intermediate acrylic/methacrylic compound may then be azo-coupledwith an appropriate diazonium salt to yield the reactive azo yellow dyesof Formula 1. Such azo coupling reactions are performed in two stages.In the first stage, an appropriate aniline compound (optionallysubstituted) is converted into a reactive diazonium salt at lowtemperatures, such as 0° to 10° C., by reaction with sodium or othersuitable nitrite salt in aqueous solution at about pH 2. In the secondstage, the reactive diazonium salt is then azo-coupled with theintermediate acrylic/methacrylic compound described above to form thedesired azo product. The azo coupling of phenolic compounds proceedsbest at a solution pH of about 4 to 8. However, with increasing reactionpH, the diazonium salt has a tendency to form byproducts via sidereactions.

These side reaction products are also phenolic compounds which cancompete with the desired intermediate acrylic/methacrylic compound inthe azo coupling reaction. As a result, changing the reactionstoichiometry from a 1:1 molar equivalence to a 4:1 excess of diazoniumsalt to acrylic/methacrylic intermediate compound is the preferred wayto synthesize Compound 1. Other reaction stoichiometries may be moreeffective in the azo coupling of other acrylic/methacrylic phenolicintermediates as determined by someone skilled in the art.

In the case of Compound 1, tyramine [4-(2-aminoethyl)phenol] acts as thephenolic starting material. It is reacted with methacrylic anhydridewithout catalytic base being necessary to give the intermediate compoundcontaining the reactive acrylic/methacrylic moiety,4-(2-methacrylamidoethyl)phenol. The azo coupling reagent is thenprepared by reacting ortho-toluidine (2-methylaniline) at about 0° C.and pH 2 with sodium nitrite in the presence of 6N hydrochloric acid.This produces the reactive diazonium salt of ortho-toluidine. Thisdiazonium salt is then reacted in situ with the phenoxide of theintermediate compound, 4-(2-methacrylamidoethyl) phenol, by azo couplingto give the preferred compound of Formula 1, Compound 1.

Also included within the scope of the present invention are thediacrylates/dimethacrylates of the formula: ##STR8## wherein R' and R"independently=H or CH₃ ;

R⁶ and R⁷ independently=R¹ ;

i and j independently=the integer 1 or 2;

R⁸, R⁹, R¹⁰ and R¹¹ independently=R⁴ ;

k and m independently=an integer from 1 to 6;

l and n independently=an integer from 0 to 6;

x=O, NH, NR⁵ ; and

R⁵ =C₁ to C₁₀ alkyl.

The preferred compound of Formula 2 isN,N-bis-(2-methacroylethyl)-(4-phenylazo)aniline: ##STR9##

Compound 2 may be prepared by the azo coupling reaction of aniline(optionally substituted) with N-phenyldiethanolamine under conditionsdescribed above for azo coupling reactions, except that only a 1:1stoichometry is necessary for azo coupling of N-phenylamines withdiazonium salts. The azo coupling proceeds well at a pH of about 2 to 4.The diazonium salt of aniline is reacted in-situ withN-phenyldiethanolamine to give the intermediate azo dyeN-(4-phenylazo)phenyldiethanolamine (also known as Solvent Yellow 58).The dimethacrylate derivative can then be prepared by reacting theintermediate azo dye, N-(4-phenylazo)phenyldiethanolamine withmethacrylic anhydride in the presence of a weak base, such astriethylamine, to yield the reactive dimethacrylic azo yellow dye,N-(4'-phenylazo)phenyl-2-bis-(2-methacrylo)ethylamine. In addition,other stronger bases, such as sodium hydride or butyllithium, might beused to form the disodium or dilithium salt followed by reaction withmethacrylic anhydride, or other methacrylic/acrylic agent used toincorporate the polymerizable group.

As one skilled in the art would appreciate, other compounds of Formula 2may be prepared using analogous reaction sequences and correspondingstarting materials. In general, compounds of Formula 2 may be preparedby azo coupling aniline (optionally substituted) with a variety ofN-phenylamines having two pendant organic spacing groups attached to theamine functionality. The organic spacing groups contain hydroxy or aminoresidues to which acrylic/methacrylic functional groups may be bonded.

The yellow polymerizable dyes of the present invention may beincorporated in a number of materials in a variety of applications whereit is desirable to block blue light (approximately 400-500 nm.). Suchapplications may include, for example, contact lenses, eyeglasses andsunglasses. A preferred application is the use of yellow polymerizabledyes in intraocular lenses. As such, one embodiment of the presentinvention is an intraocular lens containing one or more polymerizableyellow dyes ("blue-blocking IOLs").

The blue-blocking IOLs of this invention may be made by co-polymerizingone or more lens-forming monomers with one or more polymerizable yellowdyes of Formula 1 or 2. In a preferred embodiment, these monomers arecured directly in a polypropylene mold so that a finished optic isproduced. The time and temperature for curing vary with the particularlens-forming material chosen. The optic may be combined in a number ofknown ways with a variety of known haptics to produce an IOL.

The total amount of yellow dye used to form a blue-blocking IOL istypically less than about 1 wt. %. Preferably, the total amount ofyellow dye is less than about 0.25 wt. %, and most preferably, the totalamount of yellow dye is less than about 0.1 wt. %.

Suitable lens-forming monomers for use in the present invention includemethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethylmethacrylate, 3-hydroxypropyl acrylate, 3-hydroxypropyl methacrylate,n-vinyl pyrolidone, styrene, eugenol (4-hydroxyvinylbenzene),α-methylstyrene. In addition, for high-refractive index foldable lensapplications, suitable monomers include, but are not limited to:2-ethylphenoxy methacrylate, 2-ethylphenoxy acrylate, 2-ethylthiophenylmethacrylate, 2-ethylthiophenylacrylate, 2-ethylaminophenylmethacrylate, phenyl methacrylate, benzyl methacrylate, 2-phenylethylmethacrylate, 3-phenylpropyl methacrylate, 4-phenylbutyl methacrylate,4-methylphenyl methacrylate, 4-methylbenzyl methacrylate,2-2-methylphenylethyl methacrylate, 2-3-methylphenylethyl methacrylate,2-4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethylmethacrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate,2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenyl)ethylmethacrylate, 2-(2-chlorophenyl)ethyl methacrylate,2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethylmethacrylate, 2-(4-bromophenyl)ethyl methacrylate,2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethylmethacrylate), 2-(4-benzylphenyl)ethyl methacrylate, and the like,including the corresponding methacrylates and acrylates. N-vinylpyrolidone, styrene, eugenol and α-methyl styrene may also be suitablefor high-refractive index foldable lens applications. A preferredlens-forming monomer mixture is the mixture of 2-phenylethylmethacrylate (PEMA) and 2-phenylethyl acrylate (PEA).

The copolymerizable cross-linking agent used in the lens-materials ofthis invention may be any terminally ethylenically unsaturated compoundhaving more than one unsaturated group. Suitable cross-linking agentsinclude, for example: ethylene glycol dimethacrylate, diethylene glycoldimethacrylate, allyl methacrylate, 1,3-propanediol dimethacrylate,allyl methacrylate, 1,6-hexanediol dimethacrylate, 1,4-butanedioldimethacrylate, and the like. A preferred cross-linking agent is1,4-butanediol diacrylate (BDDA).

Suitable crosslinkers also include polymeric crosslinkers, such as,Polyethylene glycol 1000 Diacrylate, Polyethylene glycol 1000Dimethacrylate, Polyethylene glycol 600 Dimethacrylate, Polybutanediol2000 Dimethacrylate, Polypropylene glycol 1000 Diacrylate, Polypropyleneglycol 1000 Dimethacrylate, Polytetramethylene glycol 2000Dimethacrylate, and Polytetramethylene glycol 2000 Diacrylate.

An ultra-violet absorbing material can also be included in the polymericlenses of this invention in order that the lenses may have anultraviolet absorbance approximately equivalent to that of the naturallens of the eye. The ultraviolet absorbing material can be any compoundwhich absorbs ultraviolet light, i.e., light having a wavelength shorterthan about 400 nm, but does not absorb any substantial amount of visiblelight. The ultraviolet absorbing compound is incorporated into themonomer mixture and is entrapped in the polymer matrix when the monomermixture is polymerized. Suitable ultraviolet absorbing compounds includesubstituted benzophenones, such as 2-hydroxybenzophenone, and2-(2-hydroxyphenyl)benzotriazoles. It is preferred to use an ultravioletabsorbing compound which is copolymerizable with the monomers and isthereby covalently bound to the polymer matrix. In this way possibleleaching of the ultraviolet absorbing compound out of the lens and intothe interior of the eye is minimized. Suitable copolymerizableultraviolet absorbing compounds are the substituted2-hydroxybenzophenones disclosed in U.S. Pat. No. 4,304,895 and the2-hydroxy-5-acryloxyphenyl-2H-benzotriazoles disclosed in U.S. Pat. No.4,528,311. The most preferred ultraviolet absorbing compound is2-(3'-methallyl-2'-hydroxy-5' methyl phenyl)benzotriazole, also known asortho-methallyl TinUVin P ("oMTP").

Since many ultraviolet absorbing compounds have phenolic substituents orresidues within their structure that are known to inhibitpolymerization, the less ultraviolet absorbing compound needed thebetter. Reducing the concentration of such ultraviolet absorbingcompounds can be beneficial to the lens forming process. When theultraviolet absorbing compound is oMTP, it is typically present in aconcentration of approximately 1.8 wt. %. However, depending on thespecific yellow dye chosen and the desired transmission at a givenwavelength, considerably less than 1.8 wt. % of oMTP may be required toblock the transmission of ultraviolet and blue light. The same is truefor other ultraviolet absorbing compounds: the use of a yellow dye inconjunction with an ultraviolet absorbing compound requires less of theultraviolet absorbing compound than the use of the ultraviolet absorbingcompound alone. The total amount of both ultraviolet absorbing compoundand polymerizable yellow dye required in the IOL monomer mixture toeffectively block light of about 500 nm and below may be less than 1.9wt. %. In some cases, depending on the specific ultraviolet absorbingcompound and yellow dye chosen, the total amount may be considerablyless than about 1.9 wt. %.

The lens materials of this invention are prepared by generallyconventional polymerization methods. A mixture of lens-forming,ultraviolet absorbing and blue light blocking monomers in the desiredproportions together with a conventional thermal free-radical initiatoris prepared. The mixture can then be introduced into a mold of suitableshape to form the lens, and the polymerization carried out by gentleheating to activate the initiator. Typical thermal free radicalinitiators include peroxides, such as benzyl peroxide, peroxycarbonates,such as bis-(4-t-butylcyclohexyl)peroxydicarbonate, azonitriles, such asazo-bis-(isobutyronitrile) (AIBN), and the like. A preferred initiatoris bis-(4-t-butylcyclohexyl peroxydicarbonate) (PERK). Alternatively,the monomers can be photopolymerized by using a mold which istransparent to actinic radiation of a wavelength capable of initiatingpolymerization of these acrylic monomers by itself. Conventionalphotoinitiator compounds, e.g., a benzophenone-type photoinitiator, canalso be introduced to facilitate the polymerization. Photosensitizerscan be introduced as well to permit the use of longer wavelengths;however, in preparing a polymer which is intended for long residencewithin the eye, it is generally preferable to keep the number ofingredients in the polymer to a minimum to avoid the presence ofmaterials which might leach from the lens into the interior of the eye.

The polymerizable yellow dyes of this invention may also be used in lenscoatings. Such coatings are produced by polymerizing the monomeric dyesof this invention with soluble polymers and casting them ontotransparent materials. After coating and evaporation of the polymersolvent, such polymer solutions would impart a yellow film onto thetransparent material and give the material blue light protectiveproperties. Also, the polymerizable yellow dyes of this invention can bedissolved into a suitable monomer formula, cast onto a transparentmaterial, and cured by a suitable free-radical initiation procedure,such as exposure to heat or UV radiation. A common technique for castingsuch polymer or monomer solutions might include the spin castingtechnique for applying thin films to surfaces.

The polymerizable yellow dyes of this invention might also be dissolvedinto a suitable solvent or monomer formula, followed by immersion of thetransparent material into the dye solution. The transparent materialwould then imbibe the dye into its matrix by absorbing the solution andswelling. The curing of the polymerizable dyes can be accomplished byheat, radiation or other means suitable to bond the dye into thepolymer.

The invention will be further illustrated by the following exampleswhich are intended to be illustrative, but not limiting.

EXAMPLE 1

Preparation of Compound 1

Step one: Synthesis of Compound 1 Precursor

Into a reaction flask was added 4.4834 g (32.68 mmoles) of tyramine and100 mL of methanol. The tyramine was dissolved with stirring andsonnication. To the reaction flask was added 5.089 g (33.01 mmoles) ofmethacrylic anhydride (MAA) dropwise with constant stirring. Thereaction was performed at room temperature and was monitored by highperformance liquid chromatorgraphy (HPLC). Within the first hour afterthe MAA addition, the reaction was completed.

To the reaction flask was added 100 mL of 10% Aq. NaCl and an additional30 g of salt was added to the flask. The excess salt was filtered offand the reaction flask was cooled overnight in a freezer. The nextmorning a white solid precipitate was filtered from the reactionsolution and was washed with cold 50:50 methanol:water solution. Theliquid supernatent was cooled again to obtain a second crop of crystals.After filtering the second crop, all the solid precipitant was combinedtogether and 5.6668 g (27.61 mmoles) of Compound 1 precursor product wasobtained, Yield=84.5%.

The product was recrystallized from CHCl₃. The solid product wasfiltered off, dried in air and had a melting point of 123° C. The MP fortyramine starting material is 161°-163° C. The Compound 1 precursorproduct identity was confirmed by comparison of FTIR, NMR and massspectrum data to that of the tyramine starting material.

Step two: Synthesis of Compound 1 from the Compound 1 Precursor

Into a 1000 mL beaker was added 200 mL of deionized water followed by6.2 g (100 mmoles) of boric acid (H₃ BO₃). The boric acid was dissolvedwith stirring and the pH was monitored with the aid of a Orion EA940 IonAnalyzer and a Ross pH electrode. To the beaker was added dropwise 6NHCl to adjust the solution to about pH 2. o-Toluidine in the amount of2.0831 g (19.94 mmoles) was added to the beaker and the solution pH wasagain adjusted to pH 2 with the addition of 6N HCl. Ice was added to thereaction solution to cool it down to 0°-10° C.

Into a separate beaker was weighed 1.3603 g (19.71 mmoles) of sodiumnitrite, NaNO₂ and 20 mL of water. The sodium nitrite solution was addeddropwise into the reaction solution with constant stirring andmonitoring of the solution pH. The pH of the reaction was maintained atabout 1.9 to 2.2 by the addition of 6N HCl. Ice was added periodicallyto the reaction to keep the temperature at 0°-10° C. and the reactionwas stirred for about 10 minutes.

Into another beaker was placed 1.0048 g (4.90 mmoles) of Compound 1precursor, 30 mL of water and 1.96 mL of 2.5N NaOH (4.90 mmoles)solution. This solution was added dropwise into the ice-cooled reactionsolution with constant stirring. The reaction solution began to developa light yellowish-green color which grew more intense as more of theCompound 1 precursor solution was added. The reaction solution wasallowed to stir at 0°-10° C. for about 15 minutes at pH 2.0-2.5.

A 2.5N NaOH solution was added in small aliquots to the reactionsolution to bring the pH up to about 8.5. With increasing pH the yellowcolor of the reaction solution grew brighter. The reaction solution wasallowed to warm up to room temperature over about 2-3 hour timeinterval. As the solution warmed up a red solid floated on top of thesolution and the reaction began to take on an orange color. At thispoint the total reaction volume was about 900 mL. Upon warming to roomtemperature the reaction solution darkened to a red-brown color and avery dark solid. floated on the surface of the solution. To the solutionwas added 14.2 g (100 mmoles) of dibasic sodium phosphate. To thereaction solution was added 6N HCl dropwise until the pH was adjusted toabout 6.0.

The dark precipitate from the reaction solution was filtered off and wascombined with solid skimmed from the reaction solution. The solid redproduct was washed with about 400 mL of ice water and air dried on thefilter for about 20-30 minutes. From the reaction 6.121 9 g of the redsolid was obtained.

HPLC analysis of the red solid indicated that the reaction had threeproducts. The products were separated by column chromatography using asilica gel column. The column was eluted with methylene chloride (CH₂Cl₂) and acetonitrile (MeCN) mobile phases. Fractions of various coloredbands were collected as they eluted off the column and analyzed by HPLC.Fractions whose chromatograms indicated similar composition and puritywere combined. These combined fractions were separately filtered througha 0.5 μm filter via a glass syringe into separate round bottomed flasks.The flasks containing the combined fractions were sequencially placedonto a rotary evaporator and the solvents removed under vacuum with lowheating (approx. 50° C.). Upon solvent removal the products from thecombined fractions remained. The flasks containing desired products weredried at 50° C. under vacuum. The combined fractions of pure productwere re-analyzed by HPLC and also analyzed by mass spectroscopy and NMRspectroscopy to confirm its identity. Less pure fractions were purifiedby repeated column chromatography runs in the same manner as the aboverun until the desired product purity (>95%) was obtained.

The melting range of the product was 157°-160° C. and the amount of pureCompound 1 product obtained was 0.5153 g (1.60 mmoles), Yield=32.7%.

EXAMPLE 2

Preparation of Compound 2

Step one: Synthesis of Compound 2 Precursor by the Azo Coupling ofAniline with N-Phenyldiethanolamine

Into a 1000 mL beaker was added 200 mL of water and 14.2 g (100 mmoles)of sodium phosphate, dibasic (Na₂ HPO₄) followed by the addition of 6NHCl solution to adjust the reaction solution to pH 2. After thephosphate buffer salt was completely dissolved, 4.7351 g (50.84 mmoles)of aniline was added to the reaction solution. Ice was added to thereaction solution to cool it down to 0° C.

Into a separate beaker, 3.5151 g (50.94 mmoles) of sodium nitrite,NaNO₂, was dissolved in 20 mL of water. Ice was added to cool thesolution. The sodium nitrite solution was added dropwise with constantstirring to the reaction solution while constantly monitoring the pH ofthe reaction using a Orion EA940 Ion Analyzer and a Ross pH Electrode.The pH of the reaction was maintained to about 1.9 to 2.2 by theaddition of 6N HCl. After the addition of sodium nitrite solution wascompleted more ice was added to the reaction to keep the temperature at0°-10° C. and the reaction was stirred for about 15 minutes.

Into another beaker was placed 9.1481 g (50.48 mmoles) ofN-Phenyldiethanolamine, 100 mL of water, and enough 6N HCl was added todissolve the solid. The N-Phenyldiethanolamine solution was addeddropwise into the stirring reaction solution which was kept at 0°-10° C.by periodic addition of ice. Immediately the reaction solution began todevelop a dark red to purple color which grew more intense as more ofthe N-Phenyldiethanolamine solution was added. After the addition wascompleted the solution was stirred for about an hour and warmed up toabout 10° C. Then 50% w/v and 2N NaOH solutions were added to thereaction solution to pH 6.9. As the pH of the reaction solution rose, adark red solid precipitated out of solution. At this point the totalreaction volume was about 1 L. The solid was filtered off and washedwith water. 27.7363 g of wet precipitate was obtained.

The solid obtained from the reaction was recrystallized from amethanol:water 91:9 solution. The Compound 2 precursor product crystalswere filtered off and dried under vacuum overnight at 50° C. Theidentity of the Compound 2 precursor was confirmed by NMR and massspectroscopic analysis. Compound 2 precursor in the amount of 11.1449 g(39.06 mmoles) was obtained, melting range 136°-138° C., Yield=77.4%.

Step two: Synthesis of Compound 2 by the Reaction of Compound 2Precursor with Methacrylic Anhydride

Into a 100 mL round bottomed flask was placed 1.4299 g (5.011 mmoles) ofCompound 2 precursor and 25 mL of tetrahydrofuran (THF), completelydissolving the Compound 2 precursor. Into a tared 16×125 mm testtube wasweighed 1.5549 g (10.086 mmoles) of MAA. The MAA was then added dropwiseto the stirring reaction solution using a transfer pipet and the time ofMAA addition was noted. An HPLC analytical method was used to monitorthe progress of the reaction with time. After about four hours, 1.0452 g(10.329 mmoles) of triethylamine (Et₃ N) was added dropwise to thereaction solution. The reaction was stirred for 2 days, and then anotheraliquot of 4.1877 g (41.385 mmoles) of Et₃ N was added to the reaction.The next day, the reaction was analyzed by HPLC and another aliquot ofmethacrylic anhydride, 3.5542 g (23.054 mmoles), was added to thereaction to complete the conversion of the Compound 2 precursor toCompound 2 product.

The crude Compound 2 product was purified by column chromatography usingthe same procedure as described above for Compound 1, except that lowerheating was used for the solvent removal (30° C. instead of 50° C.).Less pure fractions and the remainder of the solid red product from thereaction were purified by repeated column chromatography runs in thesame manner as the above run until the desired product purity wasobtained. The identity of the Compound 2 product was confirmed by massspectroscopy and NMR spectroscopy.

Compound 2 is a red gum solid at room temperature and atmosphericpressure. The residual products of three synthetic attempts werecombined and purified by column chromatography. From this 1.701 g (4.04mmoles) of pure Compound 2 product was obtained from a total of 6.25 g(21.94 mmoles) of Compound 2 precursor starting material, Yield=16.4%.

EXAMPLES 3-5

Preparation of Lens Material

The bondable yellow dyes of Examples 1 and 2, were weighed intoindividual test tubes. An appropiate amount of a solution of monomerscontaining 66% PEA, 30.5% PEMA, and 3.3% BDDA by weight respectively,was added to each test tube to give a bondable yellow dye concentrationof approximately 0.1% by weight, as shown in Table 1 below: To a thirdtest tube, 15.6 mg. of 4-phenylazophenol allyl ether (a polymerizableyellow dye containing a polymerizable vinyl group) was added and anappropriate amount of the same monomer solution was added so that theyellow dye concentration was within the same range.

                  TABLE 1                                                         ______________________________________                                        Ex-   Bondable            g. PEA/PEMA                                                                              Dye Conc.                                ample Yellow Dye mg. Dye  BDDA Formula                                                                             Wt. %                                    ______________________________________                                        3     Compound 1 10.45    10.0326    0.104                                    4     Compound 2 9.67      9.0502     0.0966                                  5     4-phenylazo-                                                                             15.6     15.0049    0.104                                          phenol allyl                                                                  ether                                                                   ______________________________________                                    

After dissolving each bondable yellow dye into the PENPEMA/BDDA monomersolution an amount of bis(4-tert-butylcyclohexylperoxy dicarbonate(Perkadox-16, AZKO Corp.) was added as the polymerization iniator(catalyst) to make the initiator concentration approximately 0.5%. Onemm thick sheetstocks of the materials were made by placing theindividual bondable yellow dye/monomer solutions via syringe into moldsformed between two glass plates and a 1 mm Teflon gasket. The glassplates were held together with metal clips. Polymerization was effectedby placing the molds into a 65° C. oven and curing for 17 hours. Thetemperature of the oven was raised to 100° C. and the mold heated for 3hours to effect post-cure of the sheetstock. Rectangles measuring about1×2 cm. were cut from the sheets and soxhlet extracted for 4-5 hourswith acetone. Following extraction the material samples were dried inair followed by drying at about 50° C. under vacuum. The UV/visibletransmission and absorption spectra was measured for each example listedin Table 1 both before and after soxhlet extraction and drying. From theabsorbance of the samples at appropiate wavelengths between 400 and 500nm, the percentage of the dye which is removed in soxhlet extraction wascalculated for each example: Example 3=1%, Example 4=7% and Example5=44%. The UV/visible transmission curves for the lens materials ofExamples 3-5 (post-extraction) are shown in FIG. 1.

EXAMPLES 6-8

Dye Strength Comparison

The bondable yellow dye of Example 1 and one of the bondable yellow dyesof the Menikon Application, 2-[2'-methylphenylazo]-4-methyl-phenylmethacrylate ("Compound 3"), were weighed into test tubes according tothe amounts listed in Table 2 below. An appropriate amount of a solutionof monomers containing 66% PEA, 30.5% PEMA, and 3.3% BDDA by weight, wasadded to two of the test tubes to form the lens materials of Examples 6and 8. The lens material of Example 7 was formed by adding anappropriate amount of the following solution of monomers: 65% PEA, 30%PEMA, 3.2% BDDA and 1.8% MTP (a UV absorber). ##STR10##

                  TABLE 2                                                         ______________________________________                                        Ex-   Bondable             g. monomer                                                                             Dye Conc.                                 ample Yellow Dye mg. Dye   solution Wt. %                                     ______________________________________                                        6     Compound 3 16.4      9.9708   0.164                                     7     Compound 3 40.7      9.9862   0.406                                     8     Compound 1 14.78     10.0174  0.147                                     ______________________________________                                    

After dissolving each bondable yellow dye into the indicated monomersolution, an amount of bis(4-tert-butylcyclohexylperoxy dicarbonate)(Perkadox-16, AZKO Corp.) was added as the polymerization iniator(catalyst) to make the initiator concentration approximately 0.5% forExamples 6 and 8 and 1.0% for Example 7. One-mm thick sheetstocks of thematerials were made by placing the individual bondable yellowdye/monomer solutions via syringe into molds formed between two glassplates and a 1 mm Teflon gasket. The glass plates were held togetherwith metal clips. For Examples 6 and 7, polymerization was effected byplacing the molds into a 65° C. oven and curing for 15-17 hours with apost-cure at 100° C. for 2-3 hours. Example 8 was cured at 65° C. for1.5 hrs. with a post-cure at 100° C. for 2 hrs. Rectangles measuringapproximately 1×2 cm. were cut from the sheets and Examples 6 and 8 weresoxhlet extracted for 4-5 hours with acetone. Following extraction thematerial samples of Examples 6 and 8 were dried in air and then undervacuum at about 50° C. Example 7 was not extracted. The UV/visibletransmission and absorption spectra for each example listed above inTable 2 are shown in FIG. 2.

The dye strength of the yellow dyes in Examples 6-8 can be judged bycomparing their transmission values at wavelengths in the blue lightregion, 400-500 nm. As shown in FIG. 2, Example 6 (0.164 wt. % ofCompound 3) transmitted 53.1% at a wavelength of 450 nm. Example 7(0.406 wt. % of Compound 3) transmitted 23.8% at this wavelength, andExample 8 (0.147 wt. % of Compound 1) transmitted only 8.3%.

Comparing Examples 6 and 8 which have approxiamately the sameconcentration of dye (0.164 wt. % vs. 0.147 wt. %), Compound 1 blocksalmost 45% more light at 450 nm than does Compound 3.

Comparing Examples 7 and 8, Compound 1 blocks approximately 91.7% oflight at 450 nm while more than twice as much of the Compound 3 (0.147wt. % vs. 0.406 wt. %) blocks only approximately 76.2%.

EXAMPLES 9-10

Preparation of Finished IOLs Containing Compounds 1 & 2.

The bondable yellow dyes of Examples 1 and 2 were weighed intoindividual test tubes. To each test tube an appropiate amount of asolution of monomers containing 65% PEA, 30% PEMA, 3.2% BDDA and 1.8%oMTP by weight to give a bondable yellow dye concentration ofapproximately 0.05 and 0.2% by weight respectively, as shown in Table 3below:

                  TABLE 3                                                         ______________________________________                                        Ex-   Bondable             g. monomer                                                                             Dye Conc.                                 ample Yellow dye mg. Dye   formula  Wt. %                                     ______________________________________                                         9    Compound 1 4.0        8.0326  0.0498                                    10    Compound 2 92.4      47.3194  0.195                                     ______________________________________                                    

After dissolving the bondable yellow dye into the PEA/PEMA/BDDA/oMTPmonomer formula an amount of bis(4-tert-butylcyclohexylperoxydicarbonate (Perkadox-16, AZKO Corp.) was added as the polymerizationinitiator (catalyst) to make the initiator concentration approximately1.8 wt. %. Lens optics of the materials were made by placing theindividual bondable yellow dye/monomer solutions via syringe intopolypropylene molds which formed lenses having a refractive power of 20diopters with a central thickness of approximately 1 mm and a diameterof approximately 6 mm. For the samples of Example 9 the casting wasperformed on a plate assembly designed to hold up to. 16 polypropylenelens molds held together between the plate and spring compressed metaldies so that as many as 16 lenses could be formed simutaneously. Thesamples of Example 10 were cast into lens molds and held togetherindividually with metal clips. Polymerization was effected by placingthe molds into a 80° C. oven and curing for 1 hour. The temperature ofthe oven was raised to 100° C. and the mold heated for 1 hour to effectpost-cure of the lenses. Following curing the polypropylene lens moldsand optic were lathe cut to just less than the optic diameter to give anedge thickness of approximately 0.3 mm. Short holes approximately 1 mmdeep were drilled into opposite sides of the lens for haptic attachment.The lathed polypropylene lens molds and optic were cooled in a freezerat -5° C. for about 30 min. and then carefully split apart while stillcold. The lens optics removed from the polypropylene molds were placedinto individual tissue capsules. The lens optics were soxhlet extractedfor 4-5 hours with acetone. Following extraction the material sampleswere dried in air followed by drying at about 50° C. under vacuum. Twohaptics composed of a flexible plastic fiber material such aspolypropylene (Prolene) or of a flexible plastiized nonofilament PMMAmaterial were attached to the lens optic using the holes drilled on eachside of the lens earlier to make a finished intraocular lens.

EXAMPLE 11

Preparation of Lens Material Containing Solvent Yellow 7

4-Phenylazophenol, [Solvent Yellow 7 (SY7)], a conventional yellow dyeobtained from Aldrich Chemical Company in the amount of 10.3 mg wasdissolved into a 10.01 g solution of monomers containing 66% PEA, 30.5%PEMA, and 3.3% BDDA by weight respectively giving a SY7 concentration of0.103 wt. %. After dissolving the SY7 into the monomer solution 52.3 mgof bis(4-tert-butylcyclohexylperoxy dicarbonate (Perkadox-16, AZKOCorp.) was added as the polymerization iniator (catalyst). One mm thicksheets were made by placing the SY7 monomer solution via syringe into amold formed between two glass plates and a 1 mm Teflon gasket. The glassplates were held together with metal clips. Polymerization was effectedby placing the mold into a 65° C. oven and curing for 17 hours. Thetemperature of the oven was raised to 100° C. and the mold heated for 3hours to effect post-cure of the sheetstock. Approximately 1×2 cm.rectangles were cut from the sheet and the UV/visible measurementsperformed. The curve exhibited a strong attentuation of the shortwavelengths of visible light in the 400 to 500 nm blue light region ofthe spectrum yielding a 50% transmission level at 473 nm. Therectangular samples were placed into individual tissue capsules andsoxhlet extracted in acetone followed by drying in air then under vacuumat 50° C. Afterwards UV/visible measurements were performed again. TheUV/visible transmission and absorption spectra were measured both beforeand after soxhlet extraction and drying. From the absorbance of thesamples, at appropiate wavelengths between 400 and 500 nm, thepercentage of the dye which is removed by soxhlet extraction was foundto be 84%.

A comparison of the incorporation efficiency of the dyes of Examples 1,2, 5 and 11 in the same lens material (66% PEA, 30.5% PEMA and 3.3% BDDAby weight) is shown in FIG. 3.

The amount of absorbance between 400-500 nm lost after extraction is anindication of the amount of dye removed from the lens material by theextraction process. Low absorbance loss for wavelengths between 400-500nm indicates that very little dye failed to copolymerize with the lensforming monomers.

FIG. 3 shows that the largest loss of absorbance between 400-500 nmafter extraction occurred with the Solvent Yellow 7 dye (84%). Incontrast, the dyes containing polymerizable groups resulted in less than50% absorption loss. Of the polymerizable dyes, 4-phenylazophenol allylether (containing a polymerizable vinyl group) resulted in a 44%absorbtion loss, while both Compounds 1 and 2 (containing polymerizablemethacrylate groups) resulted in less than 10% absorbtion loss. Asmeasured by the absorption loss at appropriate wavelengths between400-500 nm, the lens material containing Compound 2 lost approximately7% of its blue light absorption while Compound 1 lost only 1%.

I claim:
 1. A polymeric ophthalmic lens material comprising:one or morelens-forming monomers selected from the group consisting of acrylatemonomers and methacrylate monomers, and one or more polymerizable yellowdyes having from one to four polymerizable acrylate or methacrylategroups, wherein each acrylate or methacrylate group is displaced fromthe dye moiety by a spacing group according to the formula ##STR11##wherein R=H or CH₃ R⁴ =acyclic organic spacing group of up to 10 atomsconsisting of C, H, Si, O, N, P, S, Cl, Br or F, alone or in anycombination; X=O, NH or NR⁵ ; R⁵ =C₁ to C₁₀ alkyl; d, e, g, and hindependently=an integer from 0 to 3; and c and f independently=aninteger from 1 to
 4. 2. The lens material of claim 1 wherein the totalamount of yellow dye is less than about 1 wt %.
 3. The lens material ofclaim 2 wherein the total amount of yellow dye is less than about 0.25wt %.
 4. The lens material of claim 3 wherein the total amount of yellowdye is less than about 0.1 wt %.
 5. The lens material of claim 1 whereinthe lens material comprises one or more lens-forming monomers selectedfrom the group consisting of phenylethyl acrylate and phenylethylmethacrylate.
 6. The lens material of claim 1 wherein the polymerizableyellow dye is ##STR12## wherein R=H or CH₃ ;R¹ =H, C₁ to C₂₀ alkyl,OCH₃, OC₂ H₅, OC₃ H₇, or OC₄ H₉ ; a and b independently=the integer 1 or2; R² =R¹, OH, NH₂, NHR⁵, N(R⁵)₂, SH, SR⁵, OR⁵, OSi(R⁵)₃, or Si(R⁵)₃ ;R⁴ =an acyclic organic spacing group of up to 10 atoms consisting of C,H, Si, O, N, P, S, Cl, Br or F, alone or in any combination; X=O, NH orNR⁵ ; R⁵ =C₁ to C₁₀ alkyl; d, e, g, and h independently=an integer from0 to 3; and c and f independently=an integer from 1 to
 4. 7. The lensmaterial of claim 6 wherein the polymerizable yellow dye is ##STR13## 8.The lens material of claim 7 wherein the material comprises less thanabout 0.1 wt. % N-2-[3-(2'-methylphenylazo)-4-hydroxyphenyl]ethylmethacrylamide, and wherein less than about 10% of the material's bluelight absorbancy is lost if the material is extracted with a solvent. 9.The lens material of claim 1 wherein less than about 10% of thematerial's blue light absorbancy is lost if the material is extractedwith a solvent.
 10. The lens material of claim 1 further comprising anultraviolet absorbing compound.
 11. The lens material of claim 10wherein the total amount of polymerizable yellow dye and ultravioletabsorbing compound is less than about 1.9 wt. %.